马来酸氟吡汀中杂质D14461及其氟吡汀二聚物的合成研究  

Synthesis of impurities D14461 and the polymer of flupirtine in flupirtine maleate

作　　者：张存彦 王路锋[2] 刘畅 徐旭 ZHANG Cun-yan;WANG Lu-feng;LIU Chang;XU Xu(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;Tianjin Chasesun Pharmaceutical Co.,Ltd,Tianjin 301700,China;Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China)

机构地区：[1]天津大学化工学院,天津300072 [2]天津红日药业股份有限公司,天津301700 [3]天津药物研究院,天津300193

出　　处：《现代药物与临床》2018年第12期3087-3091,共5页Drugs & Clinic

摘　　要：目的研究马来酸氟吡汀中杂质D14461及其氟吡汀二聚物的合成研究。方法以对氟苄胺和2-氨基-3-硝基-6-氯吡啶为起始原料,通过亲核取代反应得到2-氨基-3-硝基-6对氟苄氨基吡啶(ANFP),随后经氢化还原,光照聚合一锅法反应生成两个目标化合物,经制备液相分离纯化得到纯品。结果制备了马来酸氟吡汀中的杂质D14461及其氟吡汀二聚物,利用MS、~1H-NMR和^(13)C-NMR确证了结构,质量分数分别为99.92%、99.95%,并推测了其可能的生成机制。结论杂质D14461和氟吡汀二聚物的合成和纯化为马来酸氟吡汀的杂质研究提供了理论依据。Objective To study the synthesis of impurities D14461 and the polymer of flupirtine. Methods 4-Fluorobenzylamine and 2-amino-6-chloro-3-nitropyridine were used as starting materials to synthesize 2-amino-3-nitro-6-p-fluorobenzylamino-pyridine(ANFP) by nucleophilic substitution reactions. The two target compounds were synthesized by hydrogenation reduction and photopolymerization in one-pot, and they were purified by preparative chromatography. Results The impurities D14461 and the polymer of flupirtine in flupirtine maleate were synthesized and characterized by MS, 1H-NMR, and 13C-NMR method. And the purity detected were 99.92% and 99.95%, respectively. Formation mechanism of impurities D14461 and the polymer of flupirtine were presumed. Conclusion The synthesis and purification of impurities D14461 and the polymer of flupirtine provide the theoretical basis for the study of impurities in flupirtine maleate.

关 键 词：马来酸氟吡汀 对氟苄胺 2-氨基-3-硝基-6-氯吡啶 杂质 D14461 氟吡汀二聚物 

分 类 号：R913[医药卫生—药学]